To develop innovative new strategies and also take advantage of the recent development of new candidate agents, the NIAID is seeking ideas from the scientific community on clinical research and trial opportunities to improve the treatment and prevention of drug sensitive and resistant tuberculosis (TB) with and without HIV co-infection.

Background

TB clinical research is a high priority for the NIAID. Globally, HIV and TB are the first and second most common causes of death by single infectious agents overall, and TB is the leading cause of death for HIV-infected persons. Mycobacterium tuberculosis, the causative agent of TB, is readily transmissible, with one-third of the world’s population thought to be infected. The convergence of the TB and HIV epidemics has substantially increased the incidence, difficulty of diagnosis, and associated mortality of TB, and in turn, TB accelerates progression of HIV disease. Increasing rates of drug resistance, including the emergence of multi-drug resistant (MDR) and extensively drug resistant (XDR) M. tuberculosis strains, have greatly diminished the success rate of standard therapy for TB and have significantly increased the duration and cost of treatment. Together, escalating rates of HIV-associated TB and both MDR and XDR TB threaten global TB and HIV control.

Recent progress in the discovery and development of new diagnostics, therapeutic agents, and vaccines for TB offers significant opportunities in clinical research and for clinical trials. Specifically, new agents could pave the way for the establishment of novel treatment regimens that may have high efficacy for both drug-sensitive and resistant infections with significantly decreased treatment duration and improved tolerance and adherence. New strategies for treatment of latent TB, particularly suspected drug resistant latent TB, are needed to more effectively prevent emergence of active TB, while new vaccines are needed to provide protection from infection or progression to active disease. The combination of effective therapeutics and vaccines could curtail the rapid increase in TB incidence observed in highly endemic areas that also have high rates of HIV infection. Furthermore, combining vaccination and host directed interventions with therapeutic approaches could lead to shorter therapeutic regimens and increase patient compliance.

NIAID is exploring how to utilize its global HIV clinical trials infrastructure to implement an expanded clinical research agenda for TB as well as other infectious diseases. The recompetition of this infrastructure several years from now will fully implement this expansion. In addition, NIAID would like to use its existing infrastructure to initiate additional TB research studies, within the next two to three years, to take advantage of recent developments and opportunities.

Information Requested

The NIAID welcomes comments from the scientific community at large, including academic and non-academic investigators, on the highest priority clinical research and trial opportunities and goals for diagnosis, treatment, and prevention of TB with and without HIV co-infection, including MDR and XDR infections in adults and children. We are interested in a brief description of long range research ideas/goals but also more detailed short term studies that could be initiated within the next 2-3 years. The short term studies should focus on research that can be initiated in a short period of time that will contribute to or facilitate more comprehensive research goals. The items listed below provide an outline for responses.

Describe the long term goals and short term opportunities for clinical evaluation of novel drug regimens (initially of new and currently approved classes of therapeutic agents, potentially leading to entirely novel regimens including only new classes) and vaccine candidates to improve the prevention, treatment, and cure of active and latent TB infection, as well as for defining the role and optimal use of antiretroviral therapy in TB/HIV co-infected patients.

Describe the long term goals and short term opportunities for contributing to the development and validation of improved diagnostics, surrogate markers/biomarkers, and drug sensitivity testing.

We would also appreciate your insights in the following areas:

The need for inclusion of high priority special populations in this research and related challenges.

Key requirements for capacity at clinical research sites working in the area of TB prevention and treatment, including physical infrastructure, pharmacy needs, qualifications of personnel, linkages with local TB Control Programs, access to available populations, and experience with TB and TB/HIV clinical research that will be needed to implement short term research objectives in TB. Globally, please address the most important regions that should be considered for inclusion in these clinical research activities.

Types of local, regional, or central clinical laboratory capabilities required to implement short term TB clinical research opportunities in the context of local endemic settings, and in collaboration with national or private TB and/or HIV/TB control programs.

Partnerships and collaborations that would contribute to achieving the highest priority goals for TB clinical research that can be initiated within this time frame.

While our intent is to make use of the existing HIV clinical research infrastructure, responding to this RFI does not require that the responder have any prior connection to the current HIV networks or have HIV/AIDS research experience. Suggested research studies need not involve exclusively HIV/TB co-infected patients and may be focused on TB alone.

It is preferred that responses be submitted electronically in MS Word or PDF format via e-mail to RFIResponses@niaid.nih.gov. Please mark responses with the above RFI identifier (NOT-AI-10-015) noted in the subject line.

This RFI is for planning purposes only and should not be construed as a solicitation for applications or as an obligation on the part of the Government to provide support for any identified opportunities. Please note that the Government will not pay for response preparation or the use of any information contained therein. Responses to this RFI are voluntary and may be anonymous. Acknowledgement of receipt of responses may not be made, nor will respondents be notified of the NIAID’s evaluation of the information received. No basis for claims against the NIAID shall arise as a result of a response to this request for information or the NIAID’s use of such information as either part of our evaluation process or in developing specifications for any subsequent announcement. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s). As previously indicated, the NIAID can use the information gathered to develop grant, contract, or other funding initiatives. Any proprietary information should be so marked.